This invention relates to the topical and/or systemic treatment of psoriasis, ultraviolet radiation-induced skin diseases and skin tumors, and other related conditions with a class of compounds having sesquiterpene structures, including artemisinin, dihydroartemisinin, and derivatives and analogs of these compounds.
Psoriasis is a common skin disease characterized by hyperactive keratinocytes whose metabolism is increased nine-fold. The skin lesions generally are thick scales on sharply demarcated red plaques. The involved and uninvolved skin lesions have markedly elevated levels of the regulatory proteins putrescine and spermidine and suppressed local cell mediated immunity. No current therapies, including corticosteroids, retinoids, and immunosuppressive agents are effective in curing this disease, significantly decreasing the levels of these two polyamines, or stimulating lesional cell mediated immunity.
The polyamines of concern in this invention are generally low molecular weight, long chain, cationic aliphatic compounds with multiple amine and/or imino groups. These compounds are widely distributed in nature. Putrescine, spermidine, and spermine are the major polyamines found in man.
Ultraviolet radiation is invisible light that induces a number of diseases, including polymorphous light eruption, and collagen vascular diseases. Current therapies include topical sunscreens, immunosuppressive agents, corticosteroids, and surgery or destruction of the premalignant and malignant lesions.
Pemphigoid and pemphigus are autoimmune blistering diseases whose incidence increases with age and are life threatening. Unfortunately, a significant percentage of deaths are due to massive doses of the therapeutic agents, corticosteroids and immunosuppressives.
Artemisinin or Qinghaosu is a proven systemic antimalarial agent purified from the herb Artemisia Annua. Artemisinin is a sesquiterpene lactone with a peroxide grouping that is water insoluble but is extremely safe. There are single reports from China that artemisinin was (1) virustatic against influenza virus in chick embryo, (2) beneficial in a case of systemic lupus erythematosus, (3) suppresses humoral immunity, (4) stimulates cell mediated immunity, and (5) significantly decreases levels of all three human polyamines, especialy putrescine and spermidine.
In an effort to improve water solubility and decrease recurrences, scientists have developed semisynthetic derivatives and synthetic analogs of artemisinin. These compounds display the aforementioned sought after characteristics with the added benefit of increased antimalarial activity. These compounds have never been studied for therapeutic activity in any primary skin diseases or tumors and along with artemisinin have never been used as a topical treatment for any disease.
Treating primary skin disease and tumors with topically applied drugs improves safety, therapeutic success, and is much more cost effective. All topical drugs must penetrate the stratum corneum "barrier" to be effective. Nearly all drugs do not penetrate so penetration enhancers or vehicles have been developed to cross this barrier. When combined with the active drug, a dramatic improvement in therapeutic effectiveness occurs.